Browsing by Author "Sjoberg, Marcela K."
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- ItemA novel role for the Aurora B kinase in epigenetic marking of silent chromatin in differentiated postmitotic cells PMC(2007) Sabbattini, Pierangela; Canzonetta, Claudia; Sjoberg, Marcela K.; Nikic, Svetlana; Georgiou, Andrew; Kemball-Cook, Geoffrey; Auner, Holger W.; Dillon, Niall
- ItemComparative genomics reveals that loss of lunatic fringe (LFNG) promotes melanoma metastasis(2018) Velasco-Herrera, Martin Del Castillo; van der Weyden, Louise; Nsengimana, Jeremie; Speak, Anneliese O.; Sjoberg, Marcela K.; Bishop, David Timothy; Jonsson, Goran; Newton-Bishop, Julia; Adams, David J.
- ItemIdentification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance(2018) Kazachenka, Anastasiya; Bertozzi, Tessa M.; Sjoberg, Marcela K.; Walker, Nic; Gardner, Joseph
- ItemModeling methyl-sensitive transcription factor motifs with an expanded epigenetic alphabet(2024) Viner, Coby; Ishak, Charles A.; Johnson, James; Walker, Nicolas J.; Shi, Hui; Sjoberg, Marcela K.; Shen, Shu Yi; Lardo, Santana M.; Adams, David J.; Ferguson-Smith, Anne C.; De Carvalho, Daniel D.; Hainer, Sarah J.; Bailey, Timothy L.; Hoffman, Michael M.Background: Transcription factors bind DNA in specific sequence contexts. In addition to distinguishing one nucleobase from another, some transcription factors can distinguish between unmodified and modified bases. Current models of transcription factor binding tend not to take DNA modifications into account, while the recent few that do often have limitations. This makes a comprehensive and accurate profiling of transcription factor affinities difficult. Results: Here, we develop methods to identify transcription factor binding sites in modified DNA. Our models expand the standard A/C/G/T DNA alphabet to include cytosine modifications. We develop Cytomod to create modified genomic sequences and we also enhance the MEME Suite, adding the capacity to handle custom alphabets. We adapt the well-established position weight matrix (PWM) model of transcription factor binding affinity to this expanded DNA alphabet. Using these methods, we identify modification-sensitive transcription factor binding motifs. We confirm established binding preferences, such as the preference of ZFP57 and C/EBPβ for methylated motifs and the preference of c-Myc for unmethylated E-box motifs. Conclusions: Using known binding preferences to tune model parameters, we discover novel modified motifs for a wide array of transcription factors. Finally, we validate our binding preference predictions for OCT4 using cleavage under targets and release using nuclease (CUT&RUN) experiments across conventional, methylation-, and hydroxymethylation-enriched sequences. Our approach readily extends to other DNA modifications. As more genome-wide single-base resolution modification data becomes available, we expect that our method will yield insights into altered transcription factor binding affinities across many different modifications.
- ItemOPA1 disease-causing mutants have domain-specific effects on mitochondrial ultrastructure and fusion.(2023) Cartes Saavedra, Benjamín Tomás; Lagos Quiñones, Daniel Alejandro; Macuada, Josefa; Arancibia Radich, Duxan Andrés; Burté, Florence; Sjoberg, Marcela K.; Andrés Coke, María Estela; Horvath, Rita; Yu-Wai-Man, Patrick; Hajnoczky, Gyorgy; Eisner Sagüés, Verónica RaquelInner mitochondrial membrane fusion and cristae shape depend on optic atrophy protein 1, OPA1. Mutations in OPA1 lead to autosomal dominant optic atrophy (ADOA), an important cause of inherited blindness. The Guanosin Triphosphatase (GTPase) and GTPase effector domains (GEDs) of OPA1 are essential for mitochondrial fusion; yet, their specific roles remain elusive. Intriguingly, patients carrying OPA1 GTPase mutations have a higher risk of developing more severe multisystemic symptoms in addition to optic atrophy, suggesting pathogenic contributions for the GTPase and GED domains, respectively. We studied OPA1 GTPase and GED mutations to understand their domain-specific contribution to protein function by analyzing patient-derived cells and gain-of-function paradigms. Mitochondria from OPA1 GTPase (c.870+5G>A and c.889C>T) and GED (c.2713C>T and c.2818+5G>A) mutants display distinct aberrant cristae ultrastructure. While all OPA1 mutants inhibited mitochondrial fusion, some GTPase mutants resulted in elongated mitochondria, suggesting fission inhibition. We show that the GED is dispensable for fusion and OPA1 oligomer formation but necessary for GTPase activity. Finally, splicing defect mutants displayed a posttranslational haploinsufficiency-like phenotype but retained domain-specific dysfunctions. Thus, OPA1 domain-specific mutants result in distinct impairments in mitochondrial dynamics, providing insight into OPA1 function and its contribution to ADOA pathogenesis and severity.
- ItemRoles of cholesterol and lipids in the etiopathogenesis of Alzheimer's disease(2006) Rojo, Leonel; Sjoberg, Marcela K.; Hernández, Paula; Zambrano, Cristian; Maccioni, Ricardo B.
- ItemSixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci(2018) Lilue, Jingtao; Doran, Anthony G.; Fiddes, Ian T.; Abrudan, Mónica; Armstrong, Joel; Bennett, Ruth; Chow, William; Collins, Joanna; Collins, Stephan; Sjoberg, Marcela K.; et al.
- ItemTau phosphorylation by cdk5 and Fyn in response to amyloid peptide Abeta (25-35): involvement of lipid rafts(2009) Hernández, Paula; Lee, Gloria; Sjoberg, Marcela K.; Maccioni, Ricardo B.
- ItemTau protein binds to pericentromeric DNA: a putative role for nuclear tau in nucleolar organization(2006) Sjoberg, Marcela K.; Shestakova, Elena; Mansuroglu, Zeyni; Maccioni, Ricardo B.; Bonnefoy, Eliette
- ItemThe aurora B kinase and the polycomb protein ring1B combine to regulate active promoters in quiescent lymphocytes(2013) Frangini, Alberto; Sjoberg, Marcela K.; Roman-Trufer, Mónica; Dharmalingam, Gopuraja; Haberle, Vanja; Bartke, Till; Lenhard, Boris; Malumbres, Marcos; Vidal, Miguel; Dillon, Niall
- ItemThe BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo(2015) Karreth, Florian A.; Reschke, Markus; Ruocco, Anna; Ng, Christopher; Chapuy, Bjoern; Léopold, Valentine; Sjoberg, Marcela K.; Keane, Thomas M.; Verma, Akanksha; Ala, Ugo; Tay, Yvonne; Wu, David; Seitzer, Nina; Del Castillo Velasco-Herrera, Martín; Bothmer, Anne; Fung, Jacqueline; Langellotto, Fernanda; Rodig, Scott J.; Elemento, Olivier; Shipp, Margaret A.; Adams, David J.; Chiarle, Roberto; Pandolfi, Pier Paolo